Impairment Of Right Ventricular Function Research Articles

Randomised controlled trial examining the effect of an outpatient exercise training programme on haemodynamics and cardiac MR parameters of right ventricular function in patients with pulmonary arterial hypertension: the ExPAH study protocol

IntroductionPulmonary hypertension (PH) is a potentially life-threatening condition characterised by elevated pulmonary artery pressure. Early stage PH patients are often asymptomatic. Disease progression is associated with impairment of right ventricular...

Echocardiographic Evaluation of Right Ventricular Function in the Immediate Postoperative Period after Major Pulmonary Resections: A Prospective Observational Study

ABSTRACT Aim We aimed to identify the impact through the use of standard and novel echocardiographic parameters, i.e., speckle tracking echocardiography (STE) to evaluate the right and left ventricular (LV) myocardial function in patients who underwent lung resections. Materials and methods We identified patients that underwent lobectomy or pneumonectomy at our institution in 2016 to 2017. We performed preoperative transthoracic echocardiography (TTE) in each patient and on postoperative days (PODs) 2, 7, and 30 when available. Results Of a total of 26 patients included in the study, 5 underwent pneumonectomy, while the rest underwent lobectomy. Left and right pneumonectomy was performed in 38 and 62% of the patients respectively. None of the patients had right ventricular (RV) dilation or dysfunction on preoperative echocardiograms. Postoperatively, mean LV ejection fraction (LVEF) was 52 (±7.5) %. Mean RV strain in immediate postoperative period (day 2) was –15.1% (reduction of more than 20%). None of the patients progressed to RV failure or had mortality. Estimated RV systolic pressure was 41 (±20) mm Hg. The differences in RV echocardiographic parameters were significantly different pre- and postsurgery. The RV function decreased significantly on POD 2, which improved slightly thereafter. Extent of resection and side of resection did not make a difference in the RV functions. Conclusion After lung resection, patients developed deterioration in RV function that may be reflected by any of the echocardiographic parameters used to assess RV function. Deterioration in RV function is maximum in the immediate postoperative period (day 2), which improves to preoperative level by 4 weeks. How to cite this article Bhat IH, Kumar A, Kumar B, Ganesan R, Mandal B, Dutta V. Echocardiographic Evaluation of Right Ventricular Function in the Immediate Postoperative Period after Major Pulmonary Resections: A Prospective Observational Study. J Perioper Echocardiogr 2017;5(2):42-48.

Effects of exercise training on pulmonary hemodynamics, functional capacity and inflammation in pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by severe exercise limitation mainly attributed to the impairment of right ventricular function resulting from a concomitant elevation of pulmonary vascular resistance and pressure. The unquestioned cornerstone in the management of patients with pulmonary arterial hypertension (PAH) is specific vasoactive medical therapy to improve pulmonary hemodynamics and strengthen right ventricular function. Nevertheless, evidence for a beneficial effect of exercise training (ET) on pulmonary hemodynamics and functional capacity in patients with PH has been growing during the past decade. Beneficial effects of ET on regulating factors, inflammation, and metabolism have also been described. Small case-control studies and randomized clinical trials in larger populations of patients with PH demonstrated substantial improvements in functional capacity after ET. These findings were accompanied by several studies that suggested an effect of ET on inflammation, although a direct link between this effect and the therapeutic benefit of ET in PH has not yet been demonstrated. On this background, the aim of the present review is to describe current concepts regarding the effects of exercise on the pulmonary circulation and pathophysiological limitations, as well as the clinical and mechanistic effects of exercise in patients with PH.

Right Ventricular Outflow Tract Systolic Excursion and Fractional Shortening: Can These Echocardiographic Parameters be Used for the Assessment of Right Ventricular Function?

Background:Echocardiographic right ventricular (RV) function assessment is difficult and still a gray area despite rapid advancement of imaging modalities. The aim of this study is to assess the role of echocardiographic RV outflow tract (RVOT) function in the form of RVOT fractional shortening (RVOT FS) and RVOT systolic excursion (RVOT SE) for the assessment of RV function.Methods:We studied ninety individuals divided equally into two groups. The control group included 45 normal healthy individuals and age-matched patient group included 45 patients with RV dysfunction which was defined by tricuspid annular plane systolic excursion (TAPSE) <16 mm and RV fractional area change (RV FAC) ≤35%. Echocardiography was performed to measure RVOT FS and RVOT SE and correlate them with other parameters of RV function including TAPSE, RV FAC, peak systolic velocity of the lateral tricuspid annulus (S’) using pulsed tissue Doppler, and pulmonary acceleration time (PAcT).Results:RVOT FS showed positive correlation with TAPSE (r = 0.75, P = 0.02), RV FAC (r = 0.45, P = 0.003), and PAcT (r = 0.39, P = 0.00) and negative correlation with left atrial dimensions (LADs) (r = −0.359, P = 0.017) and left ventricular end-diastolic dimensions (r = −0.304, P = 0.042). RVOT FS <32% was 93% sensitive and 98% specific to identify patients with impaired RV function. However, RVOT SE showed weak correlation with echocardiographic RV parameters. RVOT SE <5 mm was 80% sensitive and 76% specific to identify patients with impaired RV function.Conclusion:RVOT FS is a simple valuable parameter that can be used for the assessment of RV function. However, RVOT SE is less accurate than RVOT FS in RV function assessment.

Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure.

Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertrophy and failure. Wistar rats were subjected to pulmonary trunk banding to induce compensated RV hypertrophy (n = 32) or manifest RV failure (n = 32). Rats without banding served as healthy controls (n = 30). The hearts were excised and perfused in a Langendorff system and subjected to iloprost, treprostinil, epoprostenol, or MRE-269 in increasing concentrations. The effect on RV function was evaluated using a balloon-tipped catheter inserted into the right ventricle. In control hearts, iloprost, treprostinil, and MRE-269 improved RV function. The effect was, however, absent in hearts with RV hypertrophy and failure. Treprostinil and MRE-269 even impaired RV function in hearts with manifest RV failure. Iloprost, treprostinil, and MRE-269 improved RV function in the healthy rat heart. RV hypertrophy abolished the positive inotropic effect, and in the failing right ventricle, MRE-269 and treprostinil impaired RV function. This may be related to changes in prostanoid receptor expression and reduced coronary flow reserve in the hypertrophic and failing right ventricle.

Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction.

Prevalence and Correlates of Early Right Ventricular Dysfunction in Sarcoidosis and Its Association with Outcome

Right ventricular (RV) function has not been systematically assessed in sarcoidosis. The aim of this study was to assess the prevalence and associates of RV dysfunction in sarcoidosis using global longitudinal peak systolic strain (GLS). Furthermore, whether RV dysfunction was associated with clinical outcomes was investigated. A total of 88 patients with sarcoidosis (mean age, 54±13years; 51% men) without known sarcoid-related or other structural heart disease or alternative etiologies of pulmonary hypertension were retrospectively included. RV GLS was measured using two-dimensional speckle-tracking echocardiography, and patientswere stratified (using a previously defined cutoff value) as having preserved (RV GLS<-19%) or impaired (RV GLS≥-19%) RV function. An age- and gender-matched control group (n=50) was included. The main outcome was all-cause mortality or clinical heart failure (hospitalization or New York Heart Association functional class≥III and/or deterioration by one or more classes). RV GLS was significantly reduced (-20.1±4.6 vs -24.6±1.8%, P=.001) in patients compared with control subjects. Patients with impaired RV function (n=41) were older and had worse pulmonary function, worse left ventricular diastolic function, and lower tricuspid annular plane systolic excursion compared with patients with preserved RV function (n=47). Lower tricuspid annular plane systolic excursion and diabetes were independent correlates of RV GLS. Over a median follow-up period of 37months, 19 clinical end points occurred. Patients with impaired RV function were more likely to experience the clinical end point (log-rank P=.003). RV contractile dysfunction, identified using RV GLS, is common in patients with sarcoidosis without manifest cardiac involvement or pulmonary hypertension and is associated with adverse outcome. RV GLS may therefore be useful to detect sarcoidosis-related RV dysfunction at an earlier and potentially modifiable stage.

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation.

A case of progressive breathlessness post partum

A 35-year-old woman presented with rapidly progressive dyspnoea (WHO functional class III) two months after normal vaginal delivery at term, with no other symptoms. On examination, she was normotensive, with...

Tricuspid Valve Annuloplasty Reduces Weaning Time from Temporary Right Ventricular Assistance in Patients Implanted With a Left Ventricular Assist Device

Introduction: Right ventricular (RV) failure is a serious complication after implantation of a left ventricular assist device (LVAD) and may require temporary mechanical assistance. We investigated the effectiveness of tricuspid valve annuloplasty in the presence of mild-to-moderate tricuspid valve regurgitation in reducing the weaning time from temporary RV support. Methods: From 2002 to 2014, 48 patients (mean age 54 ± 7.3) underwent LVAD implantation. The intention to treat was bridge to transplantation in 40 patients and bridge to destination in eight patients. A magnetically levitated rotary pump, designed for temporary extracorporeal support, was implanted in 11 patients (group A) to support the right ventricle. In 9 patients (group B), temporary RV support was augmented by tricuspid valve annuloplasty. We compared the outcome of the two groups of patients. Results: No significant differences were identified between the two groups regarding operative risk variables. Successful weaning from mechanical RV support occurred in nine patients in group A (81 %) and eight patients in group B (88%). Weaning time was significantly shorter for group B as compared to that of group A (9 ± 2.1 days versus 21.1 ± 8.1 days; p<0.001). Conclusion: The presence of tricuspid valve regurgitation and moderate impairment of RV function may increase the risk of early complications following LVAD implantation. Our experience suggests that the associated procedure of tricuspid annuloplasty smooths the early postoperative course and may reduce the time of temporary RV support in patients with LVAD implantation.

Right Ventricular Contractile Reserve and Pulmonary Circulation Uncoupling During Exercise Challenge in Heart Failure: Pathophysiology and Clinical Phenotypes

ObjectivesRight ventricular (RV) exercise contractile reserve (RVECR), its phenotypes, and its functional correlates are among the unresolved issues with regard to the role of the right ventricle in heart failure (HF) syndrome, and understanding these issues constitutes the objective of this study. BackgroundAlthough the role of the right ventricle in HF syndrome might be fundamental, the pathophysiology of the failing right ventricle has not been extensively investigated. MethodsNinety-seven patients with HF (mean age 64 years, 70% men, mean left ventricular ejection fraction 33 ± 10%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing. RVECR and RV–to–pulmonary circulation (PC) coupling were assessed using the length-force relationship (tricuspid annular plane systolic excursion [TAPSE] vs. pulmonary artery systolic pressure) and the slope of mean pulmonary artery pressure versus cardiac output. On the basis of TAPSE, patients were categorized into 3 groups: those with TAPSE at rest ≥16 mm (group A, n = 60) and those with TAPSE at rest <16 mm, who were divided according to median TAPSE at peak exercise (15.5 mm) into 2 subgroups (group B, ≥15.5 mm, n = 19; group C, <15.5 mm, n = 18). ResultsAlthough they had similar left ventricular ejection fractions and rest RV impairment, compared with patients in group C, those in group B showed some degree of RVECR (upward shift of the length-force relationship), better RV-to-PC coupling (lower mean pulmonary artery pressure vs. cardiac output slope), and greater ventilatory efficiency (lower slope of minute ventilation to carbon dioxide output). Rest mitral regurgitation and net changes in pulmonary artery systolic pressure were the variables retained in the best regression model as correlates of RVECR. ConclusionsIn patients with HF, RVECR unmasks different phenotypes. Impaired RV function at rest might not invariably lead to unfavorable RVECR and exercise RV-to-PC coupling. Testing these variables appears useful even in more advanced stages of HF to define various clinical conditions and, most likely, to define different levels of risk.

Concurrent Left Ventricular Assist Device (LVAD) Implantation and Percutaneous Temporary RVAD Support via CardiacAssist Protek-Duo TandemHeart to Preempt Right Heart Failure.

Right ventricular failure (RVF) is an unfortunate complication that continues to limit outcomes following durable left ventricular assist device (LVAD) implantation. Despite several ‘RVF risk scores’ having been proposed, preoperative prediction of post-LVAD RVF remains a guesstimate at best. Current strategies for institution of temporary RVAD support are invasive, necessitate additional re-thoracotomy, restrict postoperative mobilization, and/or entail prolonged retention of prosthetic material in-situ. The authors propose a novel surgical strategy comprising simultaneous implantation of a permanent LVAD and percutaneous TandemHeart® plus ProtekDuo® to provide temporary RVAD support and preempt RVF in patients with impaired RV function.

Levosimendan Prevents Pressure-Overload-induced Right Ventricular Failure.

We investigated if chronic levosimendan treatment can prevent and revert pressure-overload-induced right ventricular hypertrophy and failure in rats. Right ventricular hypertrophy and failure was induced in Wistar rats by pulmonary trunk banding (PTB). The PTB rats were treated with levosimendan (3 mg·kg·d) 3 days before surgery [n = 10, prevention (PREV)], 3 weeks after surgery [n = 10, reversal (REV)] or vehicle (n = 10, VEH). Sham-operated rats received vehicle (n = 16, SHAM). Right ventricular function was evaluated 7 weeks after surgery by echocardiography, magnetic resonance imaging, pressure-volume relations, gross anatomy, and histology. PTB induced right ventricular hypertrophy and compensated heart failure evident by reduced cardiac index (CI) without extra cardiac signs of heart failure. Levosimendan treatment prevented deterioration of right ventricular function measured by CI and right ventricular ejection fraction (RVEF) (CI: VEH vs. PREV 281 ± 17 vs. 362 ± 34 mL·min·kg, P ≤ 0.05, RVEF: VEH vs. PREV 57 ± 2% vs. 68 ± 3%, P ≤ 0.01) to values similar to SHAM (CI: 345 ± 21 mL·min·kg, RVEF: 71 ± 2%). RV contractility was improved in the REV group measured by preload recruitable stroke work (VEH vs. REV 39 ± 3 vs. 66 ± 10 mmHg P ≤ 0.05). Chronic treatment with levosimendan prevents the development of right ventricular failure and improves contractility in established pressure-overload-induced right ventricular failure.

Abstract 12055: Impaired Right Ventricular Function Affects Survival After Surgical Left Ventricular Reconstruction

Introduction: The determinants of survival after surgical left ventricular reconstruction (SVR) in ischemic heart failure remain not fully elucidated. Several left ventricular (LV) parameters have been associated with prognosis. The role of right ventricular (RV) function, however, remains to be determined. Hypothesis: Impaired preoperative RV function is associated with worse outcome in patients undergoing SVR. Methods: Consecutive patients (130 patients; age 62±10 years; 79% male; LV ejection fraction [LVEF] 27±7%; urgent surgery in 22%) underwent SVR between 2006 and 2012. Biventricular function was assessed by echocardiography before surgery. Parameters of impaired RV function were RV fractional area change (RVFAC) &lt;35%, tricuspid annular plane systolic excursion (TAPSE) &lt;16mm and RV longitudinal peak systolic strain (RV LPSS) ≥-19%. The independent association between these RV functional parameters and mortality was assessed in several non-nested multivariate analyses. Furthermore, the additive effect of multiple impaired RV parameters on mortality was assessed. Results: Survival 30 days after SVR was 89%. Impaired RVFAC (HR 3.59, 95%CI 1.21-10.68, p=0.02), TAPSE (HR 2.96, 95%CI 1.05-8.35, p=0.04) and RV LPPS (HR 3.78, 95%CI 1.11-12.85, p=0.03) were independently associated with 30 day mortality, after adjusting for LVEF, the need for urgent surgery and surgery time. Moreover, a higher number of impaired RV parameters per patient was independently associated with increased mortality (HR 5.57, 95%CI 0.94-32.85, p=0.06 for 1 impaired parameter; HR 6.90, 95%CI 1.20-39.76, p=0.03 for 2 impaired parameters; HR 21.27, 95%CI 3.11-145.56, p&lt;0.01 for 3 impaired parameters). Survival curves for impaired versus normal RVFAC, TAPSE and RV LPSS respectively and for multiple impaired parameters are presented in the figure. Conclusion: Impaired pre-operative RV function is associated with increased 30 day mortality in patients undergoing SVR.

Variability of Pulmonary Regurgitation in Proportion to Pulmonary Vascular Resistance in a Porcine Model of Total Resection of the Pulmonary Valve: Implications for Early- and Long-Term Postoperative Management of Right Ventricular Outflow Tract Reconstruction With Resulting Pulmonary Valve Incompetence.

Pulmonary regurgitation (PR) is a major concern after right ventricular (RV) outflow tract surgery. We assessed the impact of physiological changes in pulmonary vasculature on hemodynamic severity of PR and RV function and their potential clinical implications for postoperative management using a porcine model with severe PR. Eight porcine models of acute PR were established by means of resection of pulmonary valve on cardiopulmonary bypass. After separation from bypass and stabilization, blood flow in the main pulmonary artery was measured by a pulsed Doppler flowmeter, and RV systolic function was assessed on the basis of RV segment shortening (RVSS), which was analyzed by sonomicrometry. In the acute PR model, we verified the impact of pulmonary vascular resistance (Rp) on pulmonary regurgitant fraction (PRF) and RV function. Pulmonary vascular resistance was changed by manipulating the level of PaCo 2 and by inhalation of nitric oxide (NO). After bypass, the mean PRF was 40% ± 5%, and there was a deterioration of RV function. Under each ventilation condition (high CO2, low CO2, and NO 20 ppm), Rp was 836 ± 207 dyne × s × cm(-5), 499 ± 125 dyne × s × cm(-5), and 340 ± 102 dyne × s × cm(-5), respectively, and PRF was 60% ± 10%, 37% ± 5%, and 24% ± 4%, respectively, under each condition. They also showed a positive correlation in all animals. Cardiac output and RVSS were decreased by hypercapnia, while they were significantly improved after NO inhalation. This study indicates that low Rp after right ventricular outflow tract reconstruction (RVOTR) resulting in acute PR is advantageous in reducing the severity of PR and RV volume load. These findings may have clinical implications for early and long-term postoperative management of patients subjected to RVOTR with resulting pulmonary valve incompetence.

Nonalcoholic Steatohepatitis Score is an Independent Predictor of Right Ventricular Dysfunction in Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease and impaired left ventricular (LV) function, yet the impact of NAFLD on right ventricular (RV) function remains unclear. We investigate the RV functional properties in patients with NAFLD. Ninety consecutive patients with the diagnosis of biopsy-proven NAFLD and 45 age- and sex-matched controls were included. All patients underwent an echocardiographic examination. RV function was evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE). Mean fibrosis stage and nonalcoholic steatohepatitis (NASH) scores were 1.3±1.1 and 5.2±1.6, respectively. NAFLD patients displayed decreased RV function compared to controls. NAFLD patients with liver fibrosis (67 patients) had significantly lower RV function assessed by GLS (global longitudinal strain) compared to patients without liver fibrosis (18.9±3.4% vs. 21.6±2.3%, P<0.001). NASH score ≥5 was associated with lower RV-GLS (18.9±3.1% vs. 21.0±3.4%, P=0.006). NASH score inversely correlated with RV-GLS (r=-0.370, P<0.001) such as patients with impaired RV-GLS (<19%) showed significantly higher NASH score compared to normal RV-GLS group (5.8±1.4 vs. 4.8±1.7, P=0.009). Logistic regression analysis revealed that NASH score was an independent predictor of impaired RV function in patients with NAFLD. Patients with NAFLD have impaired RV function. NASH score inversely correlates with RV-GLS and independently predicts impaired RV function in patients with NAFLD.

4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.

To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease. 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed. The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups. We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices.

Assessment of systemic and pulmonary arterial remodelling in women with systemic sclerosis

Objectives: Systemic sclerosis (SSc) leads to pulmonary circulation dysfunctionand there are some indications of systemic circulation impairment. We evaluated the influence of SSc on the elastic properties of large systemic arterial walls and potential correlations between systemic and pulmonary circulation involvement.Method: We examined 75 consecutive women (mean age 53.13 ± 10.1 years) with confirmed SSc [mean disease duration (DD) 7.1 ± 9.1 years] and 21 age-matched female volunteers (mean age 52.6 ± 8.3 years, ns). Pulse wave velocity (PWV) and transthoracic echocardiography were performed. SSc patients were divided into two groups according to the median of DD: ≤ 3 years (39 patients) and > 3 years (36 patients).Results: Patients with DD > 3 years had higher PWV than those with DD ≤ 3 years and controls (log PWV: 2.23 ± 0.23 vs. 2.13 ± 0.16 and vs. 2.11 ± 0.16 m/s; p = 0.028 and 0.029, respectively). In addition, echocardiographic indices showed impaired right ventricular (RV) function in the patients with DD > 3 years. Also in these SSc patients, PWV correlated with clinical and echocardiographic parameters of pulmonary circulation: age (r = 0.64, p < 0.0001), acceleration time of pulmonary ejection (AcT; r = −0.38, p = 0.021), and tricuspid regurgitation peak gradient (TRPG; r = 0.34, p = 0.04). Multiple linear regression analysis showed that PWV was independently associated with DD (β = 0.22, p = = 0.02), AcT (β = −0.215, p = 0.03), and age (β = 0.44, p < 0.001).Conclusions: In patients with SSc lasting more than 3 years, the disease is characterized by increased stiffness of the large systemic arteries. Longer duration of SSc leads simultaneously to the increased stiffness of the large systemic arteries and to the progressive impairment of RV function and its coupling to the pulmonary arterial bed.

BMPR2 mutation in cardiomyocytes impairs insulin‐dependent trafficking of CD36

In PAH, insulin resistance is associated with impaired RV function. In mouse model of PAH with mutant BMPR2, we have shown impaired fatty acid oxidation and lipid accumulation in RV cardiomyocytes. We hypothesize that in cardiomyocytes with mutant BMPR2 insulin dependent translocation of CD36, fatty acid transporter molecule, is impaired and may contribute to lipid accumulation.H9C2 cardiomyocytes were stably transfected with empty vector (control) or plasmid containing mutant BMPR2 (mutant). CD36 protein was analyzed by western and confocal microscopy at baseline (BL) and insulin stimulation (IS) at 15 minutes (m), 30m, 1 hour (h), 24h. Key intracellular insulin signaling pathway intermediates analyzed by western.At BL, CD36 was 2fold up in mutant compared to control and increased 2fold in controls at 1h of IS. In mutant, IS lead to 50% increase in CD36 from 15m to 24h. Immunolocalization studies recapitulated these findings. IS increased CD36 in the cytoplasm and plasma membrane (PM) in mutant compared to control. At BL, pAkt Ser473, a key intermediate, was 2fold up in mutant compared to control. Within 15m of IS there was 4fold increase in pAkt Ser473 in control, and droping to BL by 24h. In mutant, there was similar increase in pAkt Ser473 for 1h, before dropped to BL at 24h. In control and mutant, levels of pAkt Ser473 substrate were similar at BL. In control, IS resulted in 2 and 5fold increase in pAS160 and AS160 from 15 and 30m to 24h respectively. In mutant pAS160 increased 2fold at 15m and AS160 protein increased only slightly compared to BL.Using cardiomyocytes with mutant BMPR2, we show impaired insulin‐mediated Akt‐AS160‐CD36 trafficking resulting in enhanced CD36 translocation to PM. This altered axis may contribute to increased lipid import and cardiac lipotoxicity.1 P01 HL 108800‐01A1

Right Ventricular Function and Right-Heart Echocardiographic Response to Therapy Predict Long-term Outcome in Patients With Pulmonary Hypertension

BackgroundRight ventricular (RV) dysfunction in pulmonary hypertension (PH) is linked to adverse outcomes, but this response is considered heterogeneous because it can be associated with multiple factors. MethodsRV function of 51 PH patients was calculated by averaging peak speckle-tracking longitudinal strain from RV free-wall (RV-free), and the cutoff for RV dysfunction was predefined as RV-free ≤ 19%. Right-sided heart remodelling was assessed in terms of RV end-systolic area (RVESA) and right atrial (RA) area (RA-area). Midterm reverse remodelling was defined as a relative decrease in RVESA (ΔRVESA) and RA-area (ΔRA-area) of at least 15% at 5.7 ± 4.0 months after introduction of pulmonary artery hypertension-specific drugs. Long-term outcome was tracked for 3.0 ± 2.0 years. ResultsPatients with midterm RV and RA reverse remodelling showed more favourable long-term outcomes than those without (P = 0.01, P = 0.047, respectively). Sequential Cox models showed that a model based on hemodynamic parameters (χ2 = 0.3) was improved by the addition of RV-free (χ2 = 6.4; P = 0.01), and further improved by addition of ΔRVESA and ΔRA-area (χ2 = 28.2; P < 0.001). Furthermore, preservation of baseline RV function and midterm reverse remodelling in right-sided heart was associated with an optimal outcome: a survival rate of 100%. In contrast, absence of midterm reverse remodelling in the right-sided heart of patients with impaired baseline RV function was associated with significantly worse outcome with a survival rate of 33% (P = 0.01). ConclusionsRV function and echocardiographic right-heart reverse remodelling with therapy improves the prediction of long-term outcomes for PH patients over standard hemodynamic indices.